title: Personalized medicine for metastatic breast cancer.
abstract: OBJECTIVE
  With recent advances in DNA sequencing technology, recurrent genomic alterations can be identified in tumor samples from patients with metastatic breast cancer (MBC) to enrich clinical trials testing targeted therapies. This review provides an overview of clinically relevant genomic alterations in MBC and summarizes the recent clinical data from early phase trials of novel targeted treatments.
  
  
  RESULTS
  The clinical development of personalized treatment includes targeted agents directed against PI3K/mTOR, fibroblast growth factor receptor (FGFR), human epidermal growth factor receptor 2 (HER2), DNA repair, and cell cycle pathways. PI3K/mTOR pathway drugs are active in endocrine and trastuzumab-resistant disease. Drugs targeted at PI3K/mTOR, FGFR, and poly(ADP-ribose) polymerase show early signs of efficacy in MBC subpopulations enriched with relevant pathway aberrancies. Regimens combining targeted agents with either endocrine, anti-HER2, or chemotherapy treatments are also being studied in hormone receptor-defined and HER2-defined or pathway-enriched subgroups.
  
  
  CONCLUSIONS
  A new approach to personalized medicine for MBC that involves molecular screening for clinically relevant genomic alterations and genotype-targeted treatments is emerging. Clinical trials are needed to determine whether rare subpopulations of MBC benefit from genotype-targeted treatments.
authors.affiliation: aDrug Development Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre bDepartment of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Tom Wei-Wu
authors.initials: TW
authors.lastname: Chen
authors.forename: Philippe L
authors.initials: PL
authors.lastname: Bedard
mesh_terms: D000911:Antibodies, Monoclonal / Q000187:drug effects*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D004260:DNA Repair / Q000187:drug effects*; D066246:ErbB Receptors / Q000187:drug effects; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects; D057285:Precision Medicine / Q000379:methods / Q000639:trends; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D011065:Poly(ADP-ribose) Polymerases; D018719:Erb-b2 Receptor Tyrosine Kinases; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human; C508053:ERBB2 protein, human